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Specificity of simple hormone response elements in androgen regulated genes

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Abstract

Androgen (AR) and glucocorticoid (GR) receptors recognize a family of 15 base pair partial palindromic hormone response elements (HRE). We have studied receptor interactions with several HREs from androgen regulated genes to determine their potential to mediate a selective androgen response. Synthetic oligonucleotides corresponding to the elements were analysed for receptor binding and steroid dependent transcriptional enhancer activities. Each HRE contained the 3′ half-site sequence (5′-TGTNCT-3′) of the glucocorticoid response element (GRE) consensus sequence. HREs that countained the 5′ half-site GRE consensus sequence (5′-A/GGNACA/G-3′) had the strongest and-rogen response element (ARE) and GRE activities. In methylation interference assays, AR and GR interacted with identical base contact sites in the response elements. Two elements that deviated from the GRE consensus sequence by a single optimal base in the 5′ half, had reduced ARE activity with no significant change in GRE activity and displayed lower binding of AR than GR in mobility shift assays using purified DNA binding domain peptides. Transfections with AR/GR and GR/AR chimeras containing the N-terminal domain of one receptor linked to the DNA-binding and C-terminal domains of the other suggested that N-terminal domain functions of GR also contributed to the greater GRE than ARE activities of the response elements.

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Author notes

  1. Keith B. Marschke

    Present address: Ligand Pharmaceuticals, San Diego, CA

  2. Stuart R. Kupfer

    Present address: Washington University School of Medicine, St. Louis, MO

Authors and Affiliations

  1. Department of Pediatrics, The University of North Carolina School of Medicine, 27599-7500, Chapel Hill, North Carolina, USA

    Keith B. Marschke, Jiann-an Tan, Stuart R. Kupfer, Elizabeth M. Wilson & Frank S. French

  2. Department of Biochemistry and Biophysics, The University of North Carolina School of Medicine, 27599-7500, Chapel Hill, North Carolina, USA

    Elizabeth M. Wilson

  3. Laboratories for Reproductive Biology, The University of North Carolina School of Medicine, 27599-7500, Chapel Hill, North Carolina, USA

    Elizabeth M. Wilson

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  1. Keith B. Marschke
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Marschke, K.B., Tan, Ja., Kupfer, S.R. et al. Specificity of simple hormone response elements in androgen regulated genes. Endocr 3, 819–825 (1995). https://doi.org/10.1007/BF02935687

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